Limbal Stem Cell Transplantation: Clinical Results, Limits, and Perspectives

Abstract

Limbal stem cell deficiency (LSCD) is a clinical condition characterized by damage of cornea limbal stem cells, which results in an impairment of corneal epithelium turnover and in an invasion of the cornea by the conjunctival epithelium. In these patients, the conjunctivalization of the cornea is associated with visual impairment and cornea transplantation has poor prognosis for recurrence of the conjunctivalization. Current treatments of LSCD are aimed at replacing the damaged corneal stem cells in order to restore a healthy corneal epithelium. The autotransplantation of limbal tissue from the healthy, fellow eye is effective in unilateral LSCD but leads to depauperation of the stem cell reservoir. In the last decades, novel techniques such as cultivated limbal epithelial transplantation (CLET) have been proposed in order to reduce the damage of the healthy fellow eye. Clinical and experimental evidence showed that CLET is effective in inducing long-term regeneration of a healthy corneal epithelium in patients with LSCD with a success rate of 70%–80%. Current limitations for the treatment of LSCD are represented by the lack of a marker able to unequivocally identify limbal stem cells and the treatment of total, bilateral LSCD which requires other sources of stem cells for ocular surface reconstruction.

Holistic Approach of Swiss Fetal Progenitor Cell Banking: Optimizing Safe and Sustainable Substrates for Regenerative Medicine and Biotechnology

“…Requirements for potential transformation and widespread therapeutic use comprise safety and consistency, availability in adequate quantities, traceable characterization, sufficient inherent expansion capacity, and compatibility with acceptable delivery methods such as engineered bioscaffolds (Doyle and Griffiths, 1998;Monti et al, 2012). Diverse classes of cell sources fit these restrictive criteria, including, but without being limited to, fetal progenitor cells (FPC), embryonic stem cells (ESC), adult stem cells [adipose stem cells (ASC), bone marrow-derived mesenchymal stem cells (BM-MSC), itMSC (ischemia-tolerant mesenchymal stem cells)], neural stem cells (NSC), limbal stem cells (LSC), hematopoietic stem cells (HSC), endothelial progenitor cells (EPC), umbilical cord cells, neonatal foreskin cells, platelets, placenta, and amniotic fluid cells (Vertelov et al, 2013;Heathman et al, 2015;Mount et al, 2015;Muraca et al, 2017;Li and Maitz, 2018;Sacchetti et al, 2018;Jayaraj et al, 2019;Torres-Torrillas et al, 2019). Most available cell sources are technically demanding, as progeny cells require dedicated processing or biochemical manipulation to orient or stabilize their potency and self-renewal capacity.…”

Clinical Trials of Limbal Stem Cell Deficiency Treated with Oral Mucosal Epithelial Cells

“…Damage to this barrier leads to the development of limbal stem cell deficiency (LSCD). The process of conjunctivalization, where conjunctival epithelial cells invade and populate the corneal surface, results in neovascularization, opacification, and inflammatory cell infiltration [14][15][16]. This limbal stem cell deficiency leads to different levels of visual impairment, as reported by the international Limbal Stem Cell Deficiency Working Group [15,17,18].…”

“…Autologous grafts produce excellent results in treating the LSCD cornea because the risk of graft rejection from the transplant is reduced. However, this treatment has limitations: (1) this approach cannot be performed if the patient has bilateral LSCD, which is a challenging task for ophthalmologists [26]; (2) a risk exists of damaging the healthy cornea [14]. Donor cornea allograft treatment heavily depends on the supply of donor corneas provided by eye banks.…”

Process Development and Safety Evaluation of ABCB5+ Limbal Stem Cells as Advanced-therapy Medicinal Product to Treat Limbal Stem Cell Deficiency

“…However, as LSCs comprise only a small population among heterogenous cell populations present in the limbus [16,17] and transplantation success highly depends on the percentage of LSCs within the transplanted cells [18], a major challenge in the further development of transplantation techniques has remained: the prospective identi cation of LSCs, which would permit enrichment of the stem cell content of the transplant. Over decades, LSCs could only be identi ed retrospectively by indirect or functional characteristics including label retention, lack of expression of corneal differentiation markers such as cytokeratin (CK)3, CK12 and CK19, ability to generate holoclones, and corneal epithelial regeneration capacity after transplantation [19]. Furthermore, although the nuclear transcription factor tumor protein 63 (p63) had been shown to identify LSCs and was thus proposed as a direct LSC marker [20], prospective cell sorting-based enrichment of limbal grafts for p63 + cells is not feasible, given its nuclear localization.…”